ClinicalTrials.gov
ClinicalTrials.gov Menu

Human Papilloma Virus (HPV) Vaccine Efficacy Trial Against Cervical Pre-cancer in Young Adults With GlaxoSmithKline (GSK) Biologicals HPV-16/18

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00122681
Recruitment Status : Completed
First Posted : July 22, 2005
Results First Posted : January 20, 2010
Last Update Posted : August 20, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition: Infections, Papillomavirus
Interventions: Biological: Cervarix™
Biological: Havrix™-based investigational formulation

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of the 18729 subjects enrolled in the study, 64 subjects were not vaccinated. Within the 18665 subjects vaccinated, 21 subjects from 1 center were excluded from all analyses because of potential data discrepancies identified at this center. As a result, a total of 18644 subjects are reported as started in the participant flow.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Participant Flow:   Overall Study
    Havrix Group   Cervarix Group
STARTED   9325   9319 
COMPLETED   7811   7798 
NOT COMPLETED   1514   1521 
Adverse Event                20                16 
Lost to Follow-up                1080                1097 
Protocol Violation                7                10 
Withdrawal by Subject                257                251 
Personal reasons                150                147 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.
Total Total of all reporting groups

Baseline Measures
   Havrix Group   Cervarix Group   Total 
Overall Participants Analyzed 
[Units: Participants]
 9325   9319   18644 
Age 
[Units: Years]
Mean (Standard Deviation)
 20.0  (3.12)   20.0  (3.10)   20.0  (3.11) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      9325 100.0%      9319 100.0%      18644 100.0% 
Male      0   0.0%      0   0.0%      0   0.0% 


  Outcome Measures

1.  Primary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post-dose 3 ]

2.  Primary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection in Subjects HPV DNA Negative and Seronegative at Baseline or Overall (Any Serostatus at Baseline)   [ Time Frame: at Month 48 ]

3.  Secondary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

4.  Secondary:   Number of Subjects Reporting Solicited Local and General Symptoms   [ Time Frame: Within 7 days after any vaccination ]

5.  Secondary:   Number of Subjects Reporting Unsolicited Adverse Events   [ Time Frame: Within 30 days after any vaccination ]

6.  Secondary:   Number of Subjects Reporting Serious Adverse Events (SAEs)   [ Time Frame: Throughout the entire study period (Month 0 to Month 48) ]
  Hide Outcome Measure 6

Measure Type Secondary
Measure Title Number of Subjects Reporting Serious Adverse Events (SAEs)
Measure Description SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Time Frame Throughout the entire study period (Month 0 to Month 48)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the Total Vaccinated Cohort. The data are presented stratified by initial (Month 0) HPV-16/18 DNA status and according to HPV-16 or 18 serostatus (by ELISA).

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed   9325   9319 
Number of Subjects Reporting Serious Adverse Events (SAEs) 
[Units: Participants]
Count of Participants
   
Total     
Participants Analyzed   9325   9319 
Total   829   835 
Sero + and DNA +     
Participants Analyzed   2419   2409 
Sero + and DNA +   239   251 
Sero- and DNA-     
Participants Analyzed   6789   6804 
Sero- and DNA-   587   576 
DNA+     
Participants Analyzed   649   690 
DNA+   69   82 

No statistical analysis provided for Number of Subjects Reporting Serious Adverse Events (SAEs)



7.  Secondary:   Number of Subjects Reporting New Onset of Chronic Disease (NOCDs)   [ Time Frame: Throughout the entire study (Month 0 to 48) ]
  Hide Outcome Measure 7

Measure Type Secondary
Measure Title Number of Subjects Reporting New Onset of Chronic Disease (NOCDs)
Measure Description NOCDs include autoimmune disorders, asthma, type I diabetes, allergies.
Time Frame Throughout the entire study (Month 0 to 48)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the Total Vaccinated Cohort and stratified according to initial (Month 0) HPV-16/18 DNA Status and According to HPV-16 or -18 Serostatus.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed   9325   9319 
Number of Subjects Reporting New Onset of Chronic Disease (NOCDs) 
[Units: Participants]
Count of Participants
   
Total     
Participants Analyzed   9325   9319 
Total   307   285 
sero+ and DNA+     
Participants Analyzed   2419   2409 
sero+ and DNA+   79   79 
sero- and DNA-     
Participants Analyzed   6789   6804 
sero- and DNA-   225   201 
DNA+     
Participants Analyzed   649   690 
DNA+   21   24 

No statistical analysis provided for Number of Subjects Reporting New Onset of Chronic Disease (NOCDs)



8.  Secondary:   Number of Subjects Reporting Medically Significant Conditions   [ Time Frame: Throughout entire study period (Month 0 to Month 48) ]

9.  Secondary:   Number of Subjects With Outcome of Pregnancies, Overall and Stratified by Initial (Month 0) HPV-16/18 DNA Status and According to HPV-16 or -18 Serostatus   [ Time Frame: Throughout the entire study period (Month 0 to Month 48) ]
  Hide Outcome Measure 9

Measure Type Secondary
Measure Title Number of Subjects With Outcome of Pregnancies, Overall and Stratified by Initial (Month 0) HPV-16/18 DNA Status and According to HPV-16 or -18 Serostatus
Measure Description Pregnancy outcomes are normal infant, premature infant, abnormal infant, elective termination, therapeutic abortion, ectopic pregnancy, spontaneous abortion, still birth, lost to follow-up, no pregnancy/molar pregnancy, pregnancy ongoing.
Time Frame Throughout the entire study period (Month 0 to Month 48)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the Total Vaccinated Cohort and stratified according to initial (Month 0) HPV-16/18 DNA Status and According to HPV-16 or -18 Serostatus.

Reporting Groups
  Description
Havrix Group Subjects received 3 doses of GSK Biologicals' hepatitis A vaccine [HAV] (Havrix™-based investigational formulation) at Months 0, 1 and 6.
Cervarix Group Subjects received 3 doses of Cervarix™ (GSK Biologicals' human papillomavirus [HPV] vaccine) at Months 0, 1 and 6.

Measured Values
   Havrix Group   Cervarix Group 
Participants Analyzed   2257   2257 
Number of Subjects With Outcome of Pregnancies, Overall and Stratified by Initial (Month 0) HPV-16/18 DNA Status and According to HPV-16 or -18 Serostatus 
[Units: Subjects]
   
total, normal infant     
Participants Analyzed   2257   2257 
total, normal infant   1671   1642 
total, premature birth     
Participants Analyzed   2257   2257 
total, premature birth   66   77 
total, abnormal infant     
Participants Analyzed   2257   2257 
total, abnormal infant   22   26 
total, elective termination     
Participants Analyzed   2257   2257 
total, elective termination   228   212 
total, therapeutic abortion     
Participants Analyzed   2257   2257 
total, therapeutic abortion   1   2 
total, ectopic pregnancy     
Participants Analyzed   2257   2257 
total, ectopic pregnancy   9   20 
total, spontaneous abortion     
Participants Analyzed   2257   2257 
total, spontaneous abortion   195   205 
total, still birth     
Participants Analyzed   2257   2257 
total, still birth   11   16 
total, lost to follow-up     
Participants Analyzed   2257   2257 
total, lost to follow-up   42   41 
total, no pregnancy, molar pregnancy     
Participants Analyzed   2257   2257 
total, no pregnancy, molar pregnancy   1   4 
total, pregnancy ongoing     
Participants Analyzed   2257   2257 
total, pregnancy ongoing   11   12 
sero- DNA- (n=1553, 1540), normal infant     
Participants Analyzed   1553   1540 
sero- DNA- (n=1553, 1540), normal infant   1164   1159 
sero- DNA-, premature birth     
Participants Analyzed   2257   2257 
sero- DNA-, premature birth   42   37 
sero- DNA-, abnormal infant     
Participants Analyzed   2257   2257 
sero- DNA-, abnormal infant   15   18 
sero- DNA-, elective termination     
Participants Analyzed   2257   2257 
sero- DNA-, elective termination   162   138 
sero- DNA-, therapeutic abortion     
Participants Analyzed   2257   2257 
sero- DNA-, therapeutic abortion   0   1 
sero- DNA-, ectopic pregnancy     
Participants Analyzed   2257   2257 
sero- DNA-, ectopic pregnancy   7   13 
sero- DNA-, spontaneous abortion     
Participants Analyzed   2257   2257 
sero- DNA-, spontaneous abortion   125   134 
sero- DNA -, still birth     
Participants Analyzed   2257   2257 
sero- DNA -, still birth   8   10 
sero- DNA-, lost to follow-up     
Participants Analyzed   2257   2257 
sero- DNA-, lost to follow-up   21   21 
sero- DNA-, no pregnancy, molar pregnancy     
Participants Analyzed   2257   2257 
sero- DNA-, no pregnancy, molar pregnancy   1   3 
sero- DNA-, pregnancy ongoing     
Participants Analyzed   2257   2257 
sero- DNA-, pregnancy ongoing   8   6 
sero+ DNA+, normal infant     
Participants Analyzed   2257   2257 
sero+ DNA+, normal infant   486   464 
sero+ DNA+, premature birth     
Participants Analyzed   2257   2257 
sero+ DNA+, premature birth   24   39 
sero+ DNA+, abnormal infant     
Participants Analyzed   2257   2257 
sero+ DNA+, abnormal infant   6   8 
sero+ DNA+, elective termination     
Participants Analyzed   2257   2257 
sero+ DNA+, elective termination   62   67 
sero+ DNA+, therapeutic abortion     
Participants Analyzed   2257   2257 
sero+ DNA+, therapeutic abortion   1   1 
sero+ DNA+, ectopic pregnancy     
Participants Analyzed   2257   2257 
sero+ DNA+, ectopic pregnancy   2   7 
sero+ DNA+, spontaneous abortion     
Participants Analyzed   2257   2257 
sero+ DNA+, spontaneous abortion   68   67 
sero+ DNA+, still birth     
Participants Analyzed   2257   2257 
sero+ DNA+, still birth   3   6 
sero+ DNA+, lost to follow-up     
Participants Analyzed   2257   2257 
sero+ DNA+, lost to follow-up   21   19 
sero+ DNA+, no pregnancy, molar pregnancy     
Participants Analyzed   2257   2257 
sero+ DNA+, no pregnancy, molar pregnancy   0   1 
sero+ DNA+, pregnancy ongoing     
Participants Analyzed   2257   2257 
sero+ DNA+, pregnancy ongoing   3   6 
DNA+(n=162, 199), normal infant     
Participants Analyzed   2257   2257 
DNA+(n=162, 199), normal infant   110   131 
DNA+, premature infant     
Participants Analyzed   2257   2257 
DNA+, premature infant   5   19 
DNA+, abnormal infant     
Participants Analyzed   2257   2257 
DNA+, abnormal infant   0   0 
DNA+, elective termination     
Participants Analyzed   2257   2257 
DNA+, elective termination   21   18 
DNA+, therapeutic abortion     
Participants Analyzed   2257   2257 
DNA+, therapeutic abortion   0   1 
DNA+, ectopic pregnancy     
Participants Analyzed   2257   2257 
DNA+, ectopic pregnancy   0   2 
DNA+, spontaneous abortion     
Participants Analyzed   2257   2257 
DNA+, spontaneous abortion   18   21 
DNA+, still birth     
Participants Analyzed   2257   2257 
DNA+, still birth   0   1 
DNA+, lost to follow-up     
Participants Analyzed   2257   2257 
DNA+, lost to follow-up   7   5 
DNA+, no pregnancy, molar pregnancy     
Participants Analyzed   2257   2257 
DNA+, no pregnancy, molar pregnancy   0   0 
DNA+, pregnancy ongoing     
Participants Analyzed   2257   2257 
DNA+, pregnancy ongoing   1   1 

No statistical analysis provided for Number of Subjects With Outcome of Pregnancies, Overall and Stratified by Initial (Month 0) HPV-16/18 DNA Status and According to HPV-16 or -18 Serostatus



10.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

11.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18   [ Time Frame: at Month 48 ]

12.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

13.  Secondary:   Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types   [ Time Frame: at Month 48 ]

14.  Secondary:   Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: at Month 48 ]

15.  Secondary:   Number of Subjects Reporting Persistent Infection (12-month Definition) With HPV-16 or HPV-18   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

16.  Secondary:   Number of Subjects Reporting Persistent Infection (12-month Definition) With HPV-16 or HPV-18   [ Time Frame: at Month 48 ]

17.  Secondary:   Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

18.  Secondary:   Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: at Month 48 ]

19.  Secondary:   Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: Up to the moment when 36 cases of CIN2+ lesions associated with HPV-16 or HPV-18 infection had been detected, including at least 15 cases of CIN2+ associated with HPV-18 infection. Mean follow-up was 34.9 months post dose 3 ]

20.  Secondary:   Number of Subjects With Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen   [ Time Frame: at Month 48 ]

21.  Secondary:   Number of Seropositive Subjects for Anti-HPV-16 and Anti-HPV-18 Antibody Titers by ELISA in the Immunogenicity Subset, According to Initial (Month 0) HPV-16 or HPV-18 Serostatus   [ Time Frame: At Months 6, 7, 12, 24, 36 & 48 ]

22.  Secondary:   Anti-HPV-16 and Anti-HPV-18 ELISA Titers in the Immunogenicity Subset   [ Time Frame: At Months 6, 7, 12, 24, 36 and 48 ]

23.  Secondary:   HPV-16 and HPV-18 Seroconversion (V5/J4 Monoclonal Inhibition Test)   [ Time Frame: Month 0, 7, 12 and 24 ]

24.  Secondary:   HPV-16 and HPV-18 Geometric Mean Titers (GMT) (V5/J4 Monoclonal Inhibition Test)   [ Time Frame: Month 0, 7, 12, 24 ]

25.  Secondary:   Number of Subjects Seropositive for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA)   [ Time Frame: At Month 0, 7, 12, 24, 36 and 48 ]

26.  Secondary:   Titers for Anti-HPV-16 and Anti-HPV-18 Antibodies Using Pseudovirion Based Neutralizing Assay (PBNA)   [ Time Frame: At month 0, 7, 12, 24, 36 and 48 ]

27.  Secondary:   Geometric Mean Titers of Anti-HPV-16 in Subjects Without and With 6-month Persistent Infection   [ Time Frame: At Month 7 ]

28.  Secondary:   Number of Seroconverted Subjects for Anti-HPV-16 Without and With 6-month Persistent Infection.   [ Time Frame: At Month 7 ]

29.  Secondary:   Geometric Mean Titers of Anti-HPV-16 in Subjects Without and With 12-month Persistent Infection   [ Time Frame: At Month 7 ]

30.  Secondary:   Number of Seroconverted Subjects for Anti-HPV-16 Without and With 12-month Persistent Infection   [ Time Frame: At Month 7 ]

31.  Secondary:   Geometric Mean Titers of Anti-HPV-18 in Subjects Without and With 6-month Persistent Infection   [ Time Frame: At Month 7 ]

32.  Secondary:   Number of Seroconverted Subjects for Anti-HPV-18 Without and With 6-month Persistent Infection.   [ Time Frame: At Month 7 ]

33.  Secondary:   Geometric Mean Titers of Anti-HPV-18 in Subjects Without and With 12-month Persistent Infection   [ Time Frame: At Month 7 ]

34.  Secondary:   Number of Seroconverted Subjects for Anti-HPV-18 Without and With 12-month Persistent Infection   [ Time Frame: At Month 7 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00122681     History of Changes
Other Study ID Numbers: 580299/008
First Submitted: July 20, 2005
First Posted: July 22, 2005
Results First Submitted: November 30, 2009
Results First Posted: January 20, 2010
Last Update Posted: August 20, 2018